Gastrointestinal (GI) motility is a coordinated neuromuscular process that transports nutrients through the digestive system. C. Scarpignato, “Pharmacological Stimulation of Gastrointestinal Motility Where We Are And Where Are We Going?” Dig. Dis., 15: 112 (1997). Impaired (i.e., slowed) motility of the gastrointestinal system, which can be involved in gastroesophageal reflux disease, gastroparesis (e.g., diabetic and postsurgical), irritable bowel syndrome, ileus, and constipation (e.g., diet or opioid-induced), is one of the largest health care burdens of industrialized nations. S. D. Feighner et al., “Receptor for Motilin Identified in the Human Gastrointestinal System,” Science, 284: 2184-2188 (Jun. 25, 1999).
Growth hormone secretagogues (GHS), such as ghrelin and mimetics thereof, have been reported to stimulate gastrointestinal motility. However, the specific GHS compounds that have been studied have pharmacokinetic properties that will not allow them to be used clinically for the treatment of gastrointestinal motility. Specifically, ghrelin is a 28-amino acid peptide that is produced in the stomach. The biologically active form of ghrelin, i.e., the acylated form, has a serum half-life of only 9-13 minutes (Akamizu et al. (2004) European Journal of Endocrinology 150:447-55). Additionally, synthetic GHS compounds such as GHRP-6 have been evaluated for the ability to treat GI motility. Similar to ghrelin, GHRP-6 has a short serum half life that prohibits the use of this compound from being used to treat GI motility disorders. Bowers et al. demonstrated that the serum half life of GHRP-6 is only 20 minutes ((1992) Journal of Clinical Endocrinology and Metabolism 74:292-8).
In view of the above, an effective, physiological way to effectively stimulate motility of the gastrointestinal system is highly desirable and would be an advance in the art.